Eshelman School of Pharmacy, The University of North Carolina, Chapel Hill, NC.
Department of Medicine, The University of North Carolina, Chapel Hill, NC.
JCO Oncol Pract. 2020 Dec;16(12):793-798. doi: 10.1200/OP.20.00553. Epub 2020 Nov 16.
Fluoropyrimidines (fluorouracil, capecitabine, and other analogs) are highly used anticancer drugs worldwide. However, patients with cancer treated with these drugs might experience severe, life-threatening toxicity because of germline genetic variation in the gene. This is a genetic predisposition with an established mechanistic basis that links genetic variation in the gene to an increase in systemic drug exposure, resulting in an increased risk of toxicity. Pharmacology guidelines provide recommendations on avoiding treatment with fluoropyrimidines or reducing their dose in patients carrying genetic variants conferring an increased risk of toxicity. However, oncology societies in the United States do not recommend systematic testing. Instead, on April 30, 2020, the European Society for Medical Oncology issued a document recommending genetic testing. In this scenario of contradicting information, practicing oncologists struggle with reaching an informed decision on whether genetic testing should be applied before treatment. This is mostly due to uncertainty about the clinical relevance of genetic testing from the perspective of a practicing oncologist. To reach an informed decision, practicing oncologists need access to concise information on the genetic variants to be tested and a practitioner-friendly interpretation of the test results. We believe this information is currently lacking. To our knowledge, for the first time, we provide a single guide for health care professionals to make an evidence-based decision about testing for patients with cancer. This article provides the essential knowledge base for oncologists to have an informed discussion with their patients about the genetic testing for . This document assists practitioners in quickly evaluating whether, when, where, and how to order a genetic test.
氟嘧啶类药物(氟尿嘧啶、卡培他滨和其他类似物)在全球范围内被广泛用于治疗癌症。然而,接受这些药物治疗的癌症患者可能会因 基因的种系遗传变异而发生严重的、危及生命的毒性反应。这是一种遗传易感性,具有明确的机制基础,它将 基因的遗传变异与全身药物暴露增加联系起来,导致毒性风险增加。药理学指南就携带增加毒性风险的 基因遗传变异的患者提供了避免使用氟嘧啶类药物或减少其剂量的建议。然而,美国的肿瘤学会并不建议进行系统检测。相反,2020 年 4 月 30 日,欧洲肿瘤内科学会发布了一份文件,建议进行基因检测。在这种相互矛盾的信息情况下,临床肿瘤医生在是否应在治疗前进行基因检测方面做出明智决策方面面临着困难。这主要是由于临床肿瘤医生对基因检测的临床相关性存在不确定性。为了做出明智的决策,临床肿瘤医生需要获得关于要检测的基因变异的简明信息,以及对检测结果的便于临床医生理解的解读。我们认为目前缺乏这些信息。据我们所知,我们首次为医疗保健专业人员提供了一份单一指南,以便他们为癌症患者进行 检测做出基于证据的决策。本文为肿瘤医生提供了与患者进行 基因检测相关的知情讨论的必要知识库。本文件帮助医生快速评估是否、何时、何地以及如何进行 基因检测。